Autologous Hematopoietic Stem-Cell Transplantation for Malignant Astrocytomas and Gliomas. Original Policy Date

Transcription

1 MP Autologous Hematopoietic Stem-Cell Transplantation for Malignant Astrocytomas and Gliomas Medical Policy Section Therapy Issue 12/2013 Original Policy Date 12/2013 Last Review Status/Date Reviewed with literature search/12/2013 Return to Medical Policy Index Disclaimer Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract. Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage. Medical technology is constantly changing, and we reserve the right to review and update our policies periodically. Description Hematopoietic Stem-Cell Transplantation Hematopoietic stem-cell transplantation (SCT) refers to a procedure in which hematopoietic stem cells are infused to restore bone marrow function in cancer patients who receive bonemarrow-toxic doses of cytotoxic drugs with or without whole-body radiation therapy. Bone marrow stem cells may be obtained from the transplant recipient (autologous SCT) can be harvested from bone marrow, peripheral blood, or umbilical cord blood and placenta shortly after delivery of neonates. Although cord blood is an allogeneic source, the stem cells in it are antigenically naïve and thus are associated with a lower incidence of rejection or graft-versushost disease. Cord blood is discussed in greater detail in policy No Preparative Conditioning for Hematopoietic Stem-Cell Transplantation Autologous SCT necessitates myeloablative chemotherapy to eradicate cancerous cells from the blood and bone marrow, thus permitting subsequent engraftment and repopulation of bone marrow space with presumably normal hematopoietic progenitor cells. As a consequence, autologous SCT is typically performed as consolidation therapy when the patient s disease is in complete remission. Patients who undergo autologous SCT are susceptible to chemotherapyrelated toxicities and opportunistic infections prior to engraftment, but not graft-versus-host disease. Astrocytomas and Gliomas Diffuse fibrillary astrocytomas are the most common type of brain tumor in adults. These tumors are classified histologically into 3 grades of malignancy: grade II astrocytoma, grade III anaplastic astrocytoma, and grade IV glioblastoma multiform. Oligodendrogliomas are diffuse neoplasms that are clinically and biologically most closely related to diffuse fibrillary astrocytomas. However, these tumors generally have better prognoses than diffuse astrocytomas, with mean survival times of 10 years versus 2 3 years. In addition, oligodendrogliomas appear to be more chemosensitive than other types of astrocytomas.

2 Glioblastoma multiforme is the most malignant stage of astrocytoma, with survival times of less than 2 years for most patients. Treatment of primary brain tumors focuses on surgery, either with curative intent or optimal tumor debulking. Surgery may be followed by radiation therapy and/or chemotherapy. Survival after chemoradiotherapy is largely dependent on the extent of residual tumor after surgical debulking. Therefore, tumors arising in the midline, basal ganglia, or corpus callosum or those arising in the eloquent speech or motor areas of the cortex, which typically cannot be extensively resected, have a particularly poor outcome. Treatment of children younger than 3 years is complicated by the long-term effects of radiation therapy on physical and intellectual function. Therefore, in young children, CNS radiation is avoided whenever possible. Note: Astrocytomas and gliomas arise from the glial cells. Tumors arising from the neuroepithelium constitute a separate category of malignancies that include CNS neuroblastoma, medulloblastoma, ependymoblastomas, and pinealblastomas. Collectively these tumors may be referred to as primitive neuroectodermal tumors (PNETs). Ependymomas also arise from the neuroepithelium but, because of their more mature histologic appearance, are not considered a member of the PNET family. The use of high-dose chemotherapy in tumors arising from the neuroepithelium is addressed separately in policy No Policy Autologous hematopoietic stem-cell transplantation is investigational as a treatment of malignant astrocytomas and gliomas. (The latter diagnosis includes both glioblastoma multiforme and oligodendroglioma.) Policy Guidelines No applicable information Rationale An older policy document on use of autologous SCT for this and other malignancies was based on a 1994 TEC Assessment. (1) The Assessment concluded that evidence available at that time did not demonstrate that this procedure improved health outcomes of adult patients with highgrade glial tumors of the brain. An initial update of the 1994 TEC Assessment reviewed literature published through 1999 and confirmed the Assessment s conclusions. It noted that although there was much research interest in use of autologous SCT for glioblastoma multiforme due to its uniformly poor prognosis, the published literature was relatively scant, consisting primarily of single-institution case series. The following representative examples were cited: Bouffet and colleagues reported on a series of 22 children and young adults with high-grade gliomas treated with HDC and autologous stem-cell support. (2) The response rate was 29% with 1 complete and 3 partial responses. However, the authors concluded that survival with HDC was no better than that reported with conventional treatments. Heideman and colleagues

3 reported on a case series of 13 pediatric patients with bulky disease or recurrent disease treated with HDC plus radiotherapy. (3) While the overall response rate was 31%, the authors similarly concluded that overall survival was no better than conventional treatment regimens. Finlay and colleagues reported on a 1996 case series of 45 children and young adults with a variety of recurrent CNS tumors, including gliomas, medulloblastomas, ependymomas, and primitive neuroectodermal tumors. (4) Of the 18 patients with high-grade gliomas, the response rate was 29%. The median survival of this group was 12.7 months. Of the 5 long-term survivors, all had high-grade glioma with minimal residual disease at the time of HDC. Based in part on these results, the authors recommended aggressive surgical debulking before HDC is even considered. Studies focusing on the use of HDC in adults with glioblastoma multiforme reported results similar to those in children, i.e., HDC appeared most successful in those with minimal disease at the time of treatment, with an occasional long-term survivor. (5,6) A review by Brandes and colleagues (7) concluded that the high drug doses used in this treatment caused excessive toxicity that was not balanced by a significant improvement in survival. Similarly, Levin and co-workers (8) concluded that it was unclear whether hematopoietic SCT had a role in management of cerebral gliomas. Additional reports on small, uncontrolled series of patients with pontine gliomas, (9) recurrent oligodendrogliomas, (10) or those undergoing radiation therapy for high-grade gliomas (11) also did not suggest that this treatment improves survival. In a phase II study, Abrey and colleagues evaluated hematopoietic stem-cell transplantation in 39 patients with newly diagnosed oligodendroglioma. (12) The authors reported the median follow-up of surviving patients was 80.5 months and with 78 months progression-free survival. The overall survival median had not been reached and 18 patients (46%) had relapsed. A nonrandomized study compared survival outcomes of 27 children (age, years) with recurrent malignant astrocytomas who underwent myeloablative chemotherapy and autologous HSCT with outcomes in a matched historical cohort (n =56) that received standard chemotherapy regimens following tumor recurrence. (12) Among the 27 children who received myeloablative chemotherapy and autologous HSCT, 5 (18%) succumbed to treatment-related toxicities within approximately 2 months of transplantation, 17 (63%) had disease progression, while 5 survived and were alive a median of 11 years (range: 8 13 years) after transplantation. Overall survival rates at 4 years were 40 ± 14% for transplant patients versus 7 ± 4% with conventional chemotherapy (p =0.018, HR: 1.9; 95% CI: ). The results of this study suggest myeloablative chemotherapy with autologous HSCT can produce long-term survival among children with recurrent malignant astrocytoma. However, lack of a contemporaneous treatment comparison group precludes conclusions as to the relative efficacy of this approach update An updated literature search in August 2011 identified no controlled studies that would change the conclusions of this policy. Thus, the policy statement is unchanged. National Cancer Institute Physician Data Query (PDQ) Clinical Trials Database A search in August 2010 found 1 active Phase II trial of hematopoietic stem-cell transplantation for newly diagnosed central nervous system tumors including glioblastoma multiforme and gliosarcoma (NCT ). National Comprehensive Cancer Network (NCCN) Guidelines

4 The 2010 NCCN Guidelines on Central Nervous System Tumors (v ) do not list HSCT as a treatment option for patients with astrocytomas or gliomas. (13) References: 1. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). HDC/AuSCS for high-grade glial tumors of the brain in adults. TEC Assessments 1994; Volume 9, Tab Bouffet E, Mottolese C, Jouvet A et al. Etoposide and thiotepa followed by ABMT (autologous bone marrow transplantation) in children and young adults with high-grade gliomas. Eur J Cancer 1997; 33(1): Heideman RL, Douglass EC, Krance RA et al. High-dose chemotherapy and autologous bone marrow rescue followed by interstitial and external-beam radiotherapy in newly diagnosed pediatric malignant gliomas. J Clin Oncol 1993; 11(8): Finlay JL, Goldman S, Wong MC et al. Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. The Children s Cancer Group. J Clin Oncol 1996; 14(9): Linassier C, Benboubker L, Velut S et al. High-dose BCNU with ABMT followed by radiation therapy in the treatment of supratentorial glioblastoma multiforme. Bone Marrow Transplant 1996; 18(suppl 1): S Fernandez-Hidalgo OA, Vanaclocha V, Vieitez JM et al.high-dose BCNU and autologous progenitor cell transplantation given with intra-arterial cisplatinum and simultaneous radiotherapy in the treatment of high-grade gliomas: benefit for selected patients. Bone Marrow Transplant 1996; 18(1): Brandes AA, Palmisano V, Pasetto LM et al.high-dose chemotherapy with bone marrow rescue for high-grade gliomas in adults. Cancer Invest 2001; 19(1): Bouffet E, Raquin M, Doz F et al. Radiotherapy followed by high dose busulfan and thiotepa: a prospective assessment of high dose chemotherapy in children with diffuse pontine gliomas. Cancer 2000; 88(3): Cairncross G, Swinnen L, Bayer R et al. Myeloablative chemotherapy for recurrent aggressive oligodendroglioma. Neuro Oncol 2000; 2(2): Jakacki RI, Siffert J, Jamison C et al. Dose-intensive, time-compressed procarbazine, CCNU, vincristine (PCV) with peripheral blood stem cell support and concurrent radiation in patients with newly diagnosed high-grade gliomas. J Neurooncol 1999; 44(1); Abrey LE, Childs BH, Paleologos N et al. High-dose chemotherapy with stem cell rescue as initial therapy for anaplastic oligodendroglioma: long-term follow-up. Neuro Oncol 2006; 8(2): Finlay JL, Dhall G, Boyett JM et al. Myeloablative chemotherapy with autologous bone marrow rescue in children and adolescents with recurrent malignant astrocytoma:

5 outcome compared with conventional chemotherapy: a report from the Children s Oncology Group. Pediatr Blood Cancer 2008; 51(6): National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Central Nervous System Cancers (v ). Available online at: Last accessed August Codes Number Description CPT Management of recipient hematopoietic cell donor search and cell acquisition Blood-derived hematopoietic progenitor cell harvesting for transplantation, per collection, autologous Thawing of previously frozen harvest without washing ;thawing of previously frozen harvest without washing ;specific cell depletion with harvest, T-cell depletion ;tumor-cell depletion ;red blood cell removal ;platelet depletion ;plasma (volume) depletion ;cell concentration in plasma, mononuclear, or buffy coat layer Bone marrow, aspiration only Biopsy, needle or trocar ICD-9 Procedure Bone marrow or blood derived peripheral stemcell transplantation; autologous Bone marrow transplant, not otherwise specified

6 41.01 Autologous bone marrow transplant Autologous hematopoietic stem-cell transplant Cord blood stem cell transplant Autologous hematopoietic stem cell transplant with purging Autologous bone marrow transplant with purging Aspiration of bone marrow from donor for transplant Other therapeutic apheresis (includes harvest of stem cells) ICD-9 Diagnosis Malignant neoplasm of the brain code range HCPCS G0265 G0266 G0267 Cryopreservation, freezing and storage of cells for therapeutic use, each cell line Thawing and expansion of frozen cells for therapeutic use, each cell line Bone marrow or peripheral stem-cell harvest, modification or treatment to eliminate cell type(s) (e.g., T cells, metastatic carcinoma) Q0083, Q0084, Q0085 Chemotherapy, administer code range J9000, J9001, J9010, J9015, J9017, J9020, J9025, J9027, J9031, J9035, J9040, J9041, J9045, J9050, J9055, J9060, J9062, J9065, J9070, J9080, J9090, J9091, J9092, J9093, J9094, J9095, J9096, J9097, J9098, J9100, J9110, J9120, J9130, J9140, J9150, J9151, J9160, J9165, J9170, J9175, J9178, J9181, J9182, J9185, J9190, J9200, J9201, J9202, J9206, J9208, J9209, J9211, J9212, J9213, Chemotherapy drug code range

7 J9214, J9215, J9216, J9217, J9218, J9219, J9225, J9226, J9230, J9245, J9250, J9260, J9261, J9263, J9264, J9265, J9266, J9268, J9270, J9280, J9290, J9291, J9293, J9300, J9303, J9305, J9310, J9320, J9340, J9350, J9355, J9357, J9360, J9370, J9375, J9380, J9395, J9600, J9999 ICD-10-CM (effective 10/1/13) ICD-10-PCS (effective 10/1/13) Type of Service Place of Service S2150 C71.0-C G0, 30243X0, 30243Y0 07DQ0ZZ, 07DQ3ZZ, 07DR0ZZ, 07DR3ZZ, 07DS0ZZ, 07DS3ZZ Therapy Inpatient/Outpatient Bone marrow or blood-derived peripheral stemcell harvesting and transplantation, allogeneic or autologous, including pheresis, high-dose chemotherapy, and the number of days of posttransplant care in the global definition (including drugs; hospitalization; medical surgical, diagnostic, and emergency services) Investigational for all relevant diagnoses. There are no specific ICD-10-CM codes for astrocytoma and glioma. Malignant neoplasm of brain code range ICD-10-PCS codes are only used for inpatient services. Percutaneous transfusion, central vein, bone marrow or stem cells, autologous, code list Surgical, lymphatic and hemic systems, extraction, bone marrow, code list Index Astrocytoma, High-Dose Chemotherapy Glioblastoma Multiforme, High-Dose Chemotherapy High-Dose Chemotherapy, Astrocytoma High-Dose Chemotherapy, Glioblastoma Multiforme High-Dose Chemotherapy, Oligodendroglioma Oligodendroglioma, High-Dose Chemotherapy